The present studies are concerned with the role of growth factors such as epidermal growth factor (EGF) and those derived from rat mammary adenocarcarcinomas (mammary tumor factors,, MTF's) and their interactions with phorbol ester tumor promoters in relationship to cell growth and differentiation with respect to neoplastic transformation in vitro and in vivo. Several systems are being utilized to study the mechanism(s) by which EGF and MTF's function as modulatory agents for cellular growth and differentiation and the accentuation or attenuation of these responses by phorbol esters. A variety of biological endpoints are being examined including cell proliferation, extracellular matrix (ECM) production, phospholipid metabolism, protein kinase modulation and growth factor and phorbol ester receptor levels.